Synthesis of Benzodioxepinones and Benzoxazepinones via Tandem Oxidation and Iodolactonization of 2-O/N-tethered Alkenyl Benzaldehyde Mediated by CuI/TBHP.

An efficient methodology for the synthesis of halogenated benzodioxepinones and benzoxazecinones has been developed via tandem oxidation and iodolactonization reaction of 2-O/N-tethered alkenyl benzaldehydes mediated by CuI and tertiarybutylhydro-peroxide in acetonitrile at 70 °C in moderate to good yields. The reaction involves initial oxidation of aldehyde to acid followed by iodolactonization. Terminal propargyl ether resulted in a mixture of mono- and diiodido-3-methylene-1,4-dioxepin-5-ones. The post-synthetic modification of the reaction products leads to the formation of corresponding thiocyanate, azide, thioether, and triazole derivatives.

Mutation Spectrum of Tuberous Sclerosis Complex Patients in Indian Population.

Tuberous sclerosis complex (TSC) is a multiorgan disorder characterized by formation of hamartomas and broad phenotypic spectrum including seizures, mental retardation, renal dysfunction, skin manifestations and brain tubers. It is inherited in an autosomal dominant pattern, caused due to mutation in either TSC1 or TSC2 genes. Seizures are one of the major presenting symptoms of TSC that helps in early diagnosis. The present study describes the mutation spectrum in TSC1 and TSC2 genes in TSC patients and their association with neurocognitive-behavioral phenotypes. Ninety-eight TSC patients were enrolled for TSC genetic testing after detailed clinical and neurobehavioral assessment. Large genomic rearrangement testing was performed by multiplex ligation-dependent probe amplification (MLPA) technique for all cases and Sanger sequencing was performed for MLPA negative cases. Large rearrangements were identified in approximately 1% in TSC1 and 14.3% in TSC2 genes. The present study observed the presence of duplications in two (2%) cases, both involving TSC2/PKD1 contiguous genes which to the best of our knowledge is reported for the first time. 8.1% of small variants were identified in the TSC1 gene and 85.7% in TSC2 gene, out of which 23 were novel variations and no variants were found in six (6.1%) cases. This study provides a representative picture of the distribution of variants in the TSC1 and TSC2 genes in Indian population along with the detailed assessment of neurological symptoms. This is the largest cohort study from India providing an overview of comprehensive clinical and molecular spectrum.